Vadanem launches in Korea…draws attention as oral option

Tanabe Pharma Korea and HK Inno.N holds launch symposium in Busan

Potential shift away from ESA-centered approach… met non-inferiority criteria in clinical trials

Strengths include ease of administration and storage… “patient-tailored treatment strategies are crucial”

The treatment paradigm for renal anemia may shift from a traditional ESA-centered approach to a multi-layered structure that includes oral treatment options. Amid this trend, Tanabe Pharma Korea and HK inno.N announced the domestic launch of the renal anemia treatment ‘Vadanem (vadadustat),’ signaling potential changes in treatment strategy.

The two companies recently held a launch symposium titled ‘New Paradigm VADANEM Symposium’ at the Lotte Hotel Busan. The event featured a wide range of discussions on the mechanism of action and clinical data of HIF-PHI class therapies, as well as strategies for their application in real-world clinical practice.

A view of the ‘Vadanem’ launch symposium.

Renal anemia is a common complication in patients with chronic kidney disease (CKD), primarily caused by reduced erythropoietin (EPO) production due to impaired kidney function. Consequently, current treatment primarily relies on recombinant erythropoiesis-stimulating agents (ESAs) administered via injection.

However, since ESAs are administered subcutaneously or intravenously, limitations have been pointed out, including treatment inconvenience, adverse reactions such as increased blood pressure and vomiting, as well as storage constraints. Although long-acting formulations with improved half-lives have emerged, the inconvenience of injection-based administration remains unresolved.

Against this backdrop, oral HIF-prolyl hydroxylase inhibitors (HIF-PHIs) are emerging as a new alternative. This class of drugs works by inhibiting the enzymes that degrade hypoxia-inducible factors (HIF), thereby stimulating endogenous EPO production while simultaneously regulating iron absorption and utilization. They also offer advantages in administration convenience and storage compared to injectables.

Vadanem is an oral HIF-PHI that regulates the HIF pathway. It induces endogenous erythropoietin production and improves iron utilization efficiency through a mechanism distinct from that of conventional ESAs.

The symposium reflected this shift, highlighting the potential transition from ESA-centered treatment to a multi-layered approach that includes oral therapies.

The first day’s session focused intensively on the mechanisms of HIF-PHI-class therapies and the clinical evidence for Vadanem. Chaired by Professor Jong-soo Lee of Ulsan University College of Medicine, presentations were delivered by Professor Bong Soo Park of Inje University College of Medicine and Professor Eun-sil Koh of The Catholic University of Korea College of Medicine.

Professor Bong Soo Park of Inje University College of Medicine explained, “While ESAs supplement exogenous EPO, HIF-PHIs activate the hypoxia response pathway to induce endogenous EPO production. This represents a more physiological treatment strategy, as it also regulates iron metabolism.”

Professor Eun-sil Koh of the Catholic University of Korea College of Medicine introduced the clinical results of Vadanem, stating, “In the INNO2VATE 1 and 2 clinical trials involving dialysis patients, Vadanem demonstrated non-inferiority in terms of hemoglobin (Hb) improvement compared to the injectable drug darbepoetin alfa (brand name Nesp).”

In fact, during the primary efficacy evaluation period (weeks 24–36), the change in hemoglobin (Hb) was 10.36 g/dL for Vadanem and 10.61 g/dL for darbepoetin alfa, and in INNO2VATE 2, these values were 10.36 g/dL and 10.53 g/dL, respectively. Vadanem met the predefined non-inferiority criteria in both studies. Hb levels remained stable and showed similar trends during the long-term evaluation from weeks 40 to 52.

It also demonstrated non-inferiority compared to darbepoetin alfa in terms of the risk of major adverse cardiovascular events (MACE). In the overall population, the hazard ratio (HR) for MACE was 0.96, meeting the predefined non-inferiority criteria (FDA 1.25, EMA 1.3).

Professor Koh explained, “Consistent results were observed for individual cardiovascular events such as death, myocardial infarction, and stroke. We have established clinical evidence regarding both efficacy and safety.”

VADANEM launch symposium

During the second day’s session, titled ‘VADANEM in Practice and Beyond,’ discussions focused on how to apply the mechanisms and clinical evidence presented the previous day to actual clinical practice.

In particular, given the confirmed clinical efficacy and safety data for Vadanem, attention centered on which patient groups should be prioritized for treatment.

Professor Sungjin Chung of the Catholic University of Korea College of Medicine stated, “In patients with CKD-related anemia, various factors such as ESA hyporesponsiveness, iron deficiency, and inflammation interact in a complex manner. For this patient population, HIF-PHI agents could serve as a new treatment alternative.”

He added, “In patients with reduced ESA responsiveness, Hb control is often difficult with existing treatments. HIF-based approaches provide a clinically meaningful option.”

He further noted, “Depending on the patient’s condition, we can adopt a more flexible treatment strategy, such as switching from ESA or considering oral therapy from the outset. Given the nature of the disease, which requires long-term treatment, oral formulations are also significant in terms of adherence. Their scope of application is expected to gradually expand in practice.”

With the launch of Vadanem, attention is focused on whether HIF-PHI therapies will establish themselves as a mainstream option in Korea. The convenience of oral administration and regulation of iron metabolism are considered key factors in future changes to CKD anemia treatment strategies.

Professor Sehoon Park of Seoul National University College of Medicine predicted, “We are entering an era that requires patient-tailored approaches based on multiple options rather than a single treatment strategy. The role of HIF-PHI class therapies will expand within this trend.”